Neoadjuvant Chemotherapy for Extremity Osteosarcoma: Preliminary Results of the Rizzoli's 4th Study

Bacci, Gaetano; Ferrari, Stefano; Mercuri, Mario; Longhi, Alessandra; Capanna, Rodolfo; Tienghi, A.; A, Brach del Prever; Comandone, Alessandro; Cesari, Marilena; Bernini, Gabriella; Picci, Piero

doi:10.1080/028418698423168

Cited by 132 publications

(127 citation statements)

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“…Currently, one of the greatest obstacles to improving the survival of patients with osteosarcoma is acquired clinical resistance to chemotherapeutic agents, primarily to the three most widely used agents in the treatment of osteosarcoma -ADM, MTX, and DDP [1,22,23] . Cancer cells can utilize a number of different mechanisms to become resistant to one or more chemotherapeutic drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Depending on the drug and cellular context, factors such as drug inactivation, drug target mutation, drug target upregulation and downregulation, decreased drug uptake, increased drug elimination and DNA damage repair have all been shown to contribute to both intrinsic and acquired resistant to chemotherapy [1] . ADM is one of the most effective agents for osteosarcoma treatment [1,22,23] . Although resistance to ADM in osteosarcoma is likely to be multifactorial, P-gp is thought to be the main resistance mechanism against this agent [1,24] .…”

Section: Discussionmentioning

confidence: 99%

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Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest

et al. 2012

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Aim: Pirarubicin (THP) is recently found to be effective in treating patients with advanced, relapsed or recurrent high-grade osteosarcoma. In this study, the effects of THP on the multidrug-resistant (MDR) osteosarcoma cells were assessed, and the underlying mechanisms for the disruption of cell cycle kinetics by THP were explored. Methods: Human osteosarcoma cell line MG63 and human MDR osteosarcoma cell line MG63/DOX were tested. The cytotoxicity of drugs was examined using a cell proliferation assay with the Cell Counting Kit-8 (CCK-8). The distribution of cells across the cell cycle was determined with flow cytometry. The expression of cell cycle-regulated genes cyclin B1 and Cdc2 (CDK1), and the phosphorylated Cdc2 and Cdc25C was examined using Western blot analyses. Results: MG63/DOX cells were highly resistant to doxorubicin (ADM) and gemcitabine (GEM), but were sensitive or lowly resistant to THP, methotrexate (MTX) and cisplatin (DDP). Treatment of MG63/DOX cells with THP (200-1000 ng/mL) inhibited the cell proliferation in time-and concentration-dependent manners. THP (50-500 ng/mL) induced MG63/DOX cell cycle arrest at the G 2 /M phase in time-and concentration-dependent manners. Furthermore, the treatment of MG63/DOX cells with THP (200-1000 ng/mL) downregulated cyclin B1 expression, and decreased the phosphorylated Cdc2 at Thr 161 . Conversely, the treatment increased the phosphorylated Cdc2 at Thr 14 /Tyr 15 and Cdc25C at Ser 216 , which led to a decrease in Cdc2-cyclin B1 activity. Conclusion: The cytotoxicity of THP to MG63/DOX cells may be in part due to its ability to arrest cell cycle progression at the G 2 /M phase, which supports the use of THP for managing patients with MDR osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest

et al. 2012

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“…However, some studies reported that a combination of ADM and cisplatin may be as efficacious as more complex regimens (Bramwell et al, 1992;Souhami et al, 1997). The role of HDMTX is still controversial, but some studies have shown the same promising results (Jaffe et al, 1973;Pratt et al, 1980;Saeter et al, 1991) as those of ifosfamide (Bacci et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Carboplatin and Doxorubicin in Treatment of Pediatric Osteosarcoma: A 9-year Single Institute Experience in the Northern Region of Thailand

Choeyprasert¹,

Natesirinilkul²,

Charoenkwan³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Osteosarcoma is the most common primary bone tumor in childhood and adolescence. Carboplatin, a platinum-derived agent, is used as neoadjuvant chemotherapy for pediatric osteosarcoma because of its anti-tumor activity and had low toxicity as compared to cisplatin. Objective: To determine demographic data, prognostic factors and outcome of childhood osteosarcoma treated with a carboplatin-based chemotherapeutic protocol at Chiang Mai University. Method: A retrospective analysis was conducted on 34 osteosarcoma patients aged less than 18 years and treated between 2003 and 2011. Results: Overall limb-salvage and amputation rates were 23.5% and 70.6%, respectively. With the mean follow-up time of 29.5 months (1.5-108.9), the Kaplan-Meier analysis for 3-year disease-free survival (DFS) and 3-year overall survival (OS) were 20.2±7.7% and 47.1±9.5% respectively. Patients who had initial pulmonary metastasis were at significantly greater risk for developing recurrence (p=0.02, OR=7; 1.2-40.1) and had a tendency to have lower 3-year OS compared to those without initial pulmonary metastasis (28.1±13%, 63.1±12.3%, respectively, p=0.202). On univariate analysis, age at diagnosis >14 years and patients who were declined surgery were significantly associated with lower 3-year OS (p=0.008 and <0.05, respectively). However, age at diagnosis, sex, tumor size and histological subtypes were not found to significantly affect recurrence or survival. Conclusions: In our study, the survival rate was far lower than those reported from developed countries. These might indicate the ineffectiveness of carboplatin in combination with doxorubicin as frontline treatment of pediatric osteosarcoma, especially in those with initial pulmonary metastasis. Refinement in risk and treatment stratification and dose intensification for pediatric osteosarcoma constitutes a future challenge to improve outcomes, especially in metastatic patients who may need a more intensive regimen.

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“…By using serial arteriography to monitor tumor response and individualize the duration of neoadjuvant therapy, we achieved a 77% rate of good histologic response. We deduce that our high rate of good response likely translated into an exceptional survival rate as opposed to more traditional protocols which prescribe a set number of preoperative cycles and result in survival rates in the 70% range [1,3,4,7,19,21,24,[42][43][44]52].…”

Section: Discussionmentioning

confidence: 99%

Intraarterial Chemotherapy for Extremity Osteosarcoma and MFH in Adults

Hugate

Wilkins

Kelly

et al. 2008

Clinical Orthopaedics &Amp; Related Research

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The neoadjuvant treatment of osteosarcoma using intravenous agents has resulted in survival rates of 55% to 77% [3,5,6,20,22,35]. We designed a neoadjuvant chemotherapy protocol using combined intraarterial and intravenous agents to treat high-grade osteosarcoma and malignant fibrous histiocytoma of bone in an attempt to improve survival. We report the results of treating 53 adults (age 18-77 years) diagnosed with nonmetastatic extremity osteosarcoma or malignant fibrous histiocytoma. Preoperative chemotherapy consisted of intravenous doxorubicin followed by intraarterial cisplatinum administered repetitively every 3 weeks for three to five cycles, depending on tumor response assessed by serial arteriography. Dose and duration of cisplatin were adjusted for tumor size. After resection, good responders (90% or greater necrosis) underwent treatment with the same agents and poor responders were treated with alternative agents for longer duration. Minimum followup was 24 months (mean, 111 months; range, 24-235 months). Estimated Kaplan-Meier survival at 10 years was 82% and event-free survival was 79%. Forty-one patients (77%) had a good histologic response and 92% (49 of 53) underwent limbsparing procedures. Local recurrence occurred in two patients (4%). These results compared favorably with those reported in the current literature.

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Neoadjuvant Chemotherapy for Extremity Osteosarcoma: Preliminary Results of the Rizzoli's 4th Study

Cited by 132 publications

References 13 publications

Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest

Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest

Carboplatin and Doxorubicin in Treatment of Pediatric Osteosarcoma: A 9-year Single Institute Experience in the Northern Region of Thailand

Intraarterial Chemotherapy for Extremity Osteosarcoma and MFH in Adults

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